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    Summary
    EudraCT Number:2017-004392-32
    Sponsor's Protocol Code Number:MS100070-0028
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-05
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2017-004392-32
    A.3Full title of the trial
    CAVE (Cetuximab-AVElumab) mCRC: A single arm phase IIclinical study of the combination of avelumab plus cetuximab in pre-treated RAS wild type metastatic colorectal cancer patients.
    CAVE (Cetuximab-AVElumab) mCRC: A single arm phase IIclinical study of the combination of avelumab plus cetuximab in pre-treated RAS wild type metastatic colorectal cancer patients.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Avelumab plus Cetuximab in patients with mCRC
    Avelumab+Cetuximab in pazienti affetti da carcinoma del colon retto
    A.3.2Name or abbreviated title of the trial where available
    CAVE mCRC
    CAVE mCRC
    A.4.1Sponsor's protocol code numberMS100070-0028
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorA.O.U. Università degli Studi della Campania "Luigi Vanvitelli"
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck KGAA
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAzienda Ospedaliera Universitaria della seconda università degli studi di Napoli
    B.5.2Functional name of contact pointDipartimento Internistica Clinica e
    B.5.3 Address:
    B.5.3.1Street Addressvia pansini 5
    B.5.3.2Town/ cityNapoli
    B.5.3.3Post code80131
    B.5.3.4CountryItaly
    B.5.4Telephone number0815666760
    B.5.5Fax number0815666688
    B.5.6E-maildaniela.renato@hotmail.it
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBAVENCIO
    D.3.2Product code [MSB001071BC]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAvelumab
    D.3.9.1CAS number 1537032-82-8
    D.3.9.2Current sponsor codeMSB001071BC
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name ERBITUX - 5 MG/ML SOLUZIONE PER INFUSIONE - USO ENDOVENOSO- FLACONCINO(VETRO) 20 ML 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderMERCK KGAA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameERBITUX
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCETUXIMAB
    D.3.9.1CAS number 205923-56-4
    D.3.9.2Current sponsor codeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic colorectal cancer
    adenocarcinoma del colon-retto metastatico (mCRC) RAS wild type
    E.1.1.1Medical condition in easily understood language
    Metastatic colorectal cancer
    Tumore del colon retto metastatico
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10052358
    E.1.2Term Colorectal cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate the efficacy (OS) of avelumab and cetuximab combinedin pre-treated RAS wild type metastatic colorectal cancer patients
    L'obbiettivo principale della sperimentazione è valutare l'efficacia in termini di sopravvivenza globale (OS) di avelumab in combinazione con cetuximab nei pazienti con mCRC RAS wild type precedentemente trattati con altri regimi di trattamento
    E.2.2Secondary objectives of the trial
    To demonstrate superiority with regard to the objective response rate (ORR) of avelumab and cetuximab combined in pre-treated RAS wild type metastatic colorectal cancer patients.
    To demonstrate superiority with regard to progression free survival (PFS) of avelumab and cetuximab combined in pre-treated RAS wild type metastatic colorectal cancer patients.
    To determine the safety and tolerability of avelumab and cetuximab combinedin pre-treated RAS wild type metastatic colorectal cancer patients.
    Determinare l’efficacia in termini di tasso di risposta obiettiva (ORR) di avelumab in combinazione con cetuximab nei pazienti con mCRC RAS wild type precedentemente trattati con altri regimi di trattamento.
    Determinare l’efficacia in termini di sopravvivenza libera da progressione (PFS) di avelumab in combinazione con cetuximab nei pazienti con mCRC RAS wild type precedentemente trattati con altri regimi di trattamento.
    Determinare la sicurezza e la tollerabilità di avelumab in combinazione con cetuximab nei pazienti con mCRC RAS wild type precedentemente trattati con altri regimi di trattamento.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Histologically proven diagnosis of colorectal adenocarcinoma;

    Diagnosis of metastatic disease;

    RAS (NRAS and KRAS exon 2,3 and 4) wild-type in tissue at initial diagnosis;

    Efficacy of a first line therapy containing an anti-EGFR agent (panitumumab or cetuximab) with a major response achieved (complete or partial response);

    A second line therapy;

    More than 4 months from last dose of anti-EGFR agent administered in first line treatment before randomization;

    Measurable disease according to RECIST criteria v1.1;

    ECOG PS of 0 to 1 at trial entry;

    Estimated life expectancy of more than 12 weeks.
    Diagnosi istologica di adenocarcinoma del colon-retto;

    Diagnosi di malattia metastatica;

    RAS (NRAS e KRAS esone 2,3 e 4) wild type nel tessuto tumorale alla diagnosi;

    Efficacia di una terapia di prima linea contenente un agente anti-EGFR (panitumumab o cetuximab) dalla quale è stato ottenuta una risposta completa o parziale;

    Una seconda linea di terapia;

    Più di 4 mesi dall'ultima dose di agente anti-EGFR somministrato nel trattamento della prima linea prima della randomizzazione;

    Malattia misurabile secondo i criteri RECIST v1.1;

    ECOG PS da 0 a 1 al momento dell'ingresso nella sperimentazione;

    Aspettativa di vita stimata di più di 12 settimane.
    E.4Principal exclusion criteria
    Participation in a clinical study or experimental drug treatment within 30 days;

    Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment;

    All subjects with brain metastases, except those meeting the following criteria:
    -Brain metastases have been treated locally, and
    -No ongoing neurological symptoms that are related to the brain localization of the disease;

    Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
    Partecipazione ad uno studio clinico o trattamento farmacologico sperimentale entro 30 giorni;

    I soggetti che ricevono agenti immunosoppressivi (come gli steroidi) per qualsiasi motivo dovrebbero interrompere questi farmaci prima dell'inizio del trattamento;

    Tutti i soggetti con metastasi del cervello, ad eccezione di quelli che soddisfano i seguenti criteri:
    - Le metastasi cerebrali sono state trattate localmente e
    -assenza di sintomi neurologici legati alla localizzazione cerebrale della malattia;

    Malattia autoimmune attiva che potrebbe peggiorare quando si riceve un agente immunostimolante.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint for the trial is OS time, defined as the interval from enrollment to death for every cause.
    L'obiettivo primario della sperimentazione è l'OS, definita come l'intervallo che va dall'arruolamento del soggetto alla sua morte per qualsiasi causa.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The survival follow-up will continue until 2 years after the last subject receives the last dose of avelumab and cetuximab.
    Il follow-up della sopravvivenza continuerà per un massimo di 2 anni dopo che l'ultimo soggetto abbia ricevuto l'ultima dose di avelumab e cetuximab.
    E.5.2Secondary end point(s)
    The overall response rate (ORR) according to RECIST 1.1

    Progression free survival (PFS) according to RECIST 1.1

    The safety profile of the trial drugs as measured by the incidence of AEs, SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS.
    Il tasso di risposta obiettiva (ORR) secondo i criteri RECIST 1.1

    La sopravvivenza libera da malattia (PFS) secondo i criteri RECIST 1.1

    Il profilo di sicurezza del trattamento in studio è valutato in base all'incidenza di EA e SAE, in base alle analisi di laboratorio, ai segni vitali, all'esame obiettivo, alla valutazione del PS secondo ECOG e all'ECG.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The ORR according to RECIST 1.1
    The PFS according to RECIST 1.1
    The Safety profile of the trial drugs as meausured by the incidence of AEs, SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS.
    L'ORR in accordo con i criteri RECIST 1.1
    La PFS in accordo con i criteri RECIST 1.1
    Il profilo di sicurezza del trattamento sperimentale definito tramite la valutazione dell'incidenza di EA, SAE, valutazione dei parametri di laboratorio, segni vitali, esame obiettivo, ECG e PS secondo ECOG.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The whole trial may be discontinued prematurely in the event of any of the following:
    - New information leading to unfavorable risk-benefit judgment of the trial drug, for example, due to
    - evidence of inefficacy of the trial drug,
    - otherunfavorablesafetyfindings
    Sponsor’s decision that continuation of the trial is unjustifiable for medical or ethical reasons
    - Poor enrollment of subjects
    L'intero studio può essere prematuramente discontinuato se:
    -si rendono disponibili nuovi dati sul rapporto rischio/benefiicio non favorevole per il trattamento
    - evidenza di non efficacia del trattamento
    - altre informazioni sulla sicurezza non favorevoli
    - decisione dello sponsor basata su motivi clinici/etici
    - scarso arruolamento
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 37
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 38
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state75
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 75
    F.4.2.2In the whole clinical trial 75
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    If the trial is not terminated, the survival follow-up will continue until 2 years after the last subject receives the last dose of avelumab plus cetuximab.
    Se lo studio non terminerà prematuramente. il follow-up per la sopravvivenza continuerà fino a 2 anni dopo l'ultima somministrazione di avelumab più cetuximab per l'ultimo soggetto arruolato.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-05-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-25
    P. End of Trial
    P.End of Trial StatusOngoing
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